(500e) Developing a Hydrogel System for Controlled Release of Thymosin Beta-4 to the Corneal Epithelium

Thymosin beta-4 (TB4, Mw = 4.9 kDa) is a naturally occurring and highly conserved actin-binding protein that has been shown to promote corneal epithelial cell migration in vitro and to accelerate corneal wound healing in vivo. Conditions such as diabetes mellitus, which affects 16 million Americans, are associated with impaired wound healing in many tissues. In particular, clinical therapies that re-establish normal corneal healing are extremely limited. Towards this end, we aimed to develop a hydrogel system suitable for prolonged delivery of TB4 to the corneal epithelium. Crosslinked PEG di-acrylate (PEGDA) hydrogels were prepared from PEGDA of Mw 700 Da and 575 Da. Similarly, calcium-crosslinked alginate hydrogels were prepared at a range of concentrations. Values for the average Mw between crosslinks were determined by equilibrium swelling studies, and the binding and diffusion of TB4 to and through candidate hydrogels were characterized using both unmodified and fluorescently labeled TB4. Preliminary results suggest that both hydrogel types are suitable for achieving extended release of TB4, but hydrogel permeabilities and mechanics require optimization. Candidate materials were shown to have increasing Mw between crosslinks with decreasing material concentration. The effect of this on TB4 diffusion was seen in binding and diffusion studies. Studies aimed at optimizing TB4 release rates over 100 hours are currently ongoing, and results of the release studies and the biological activity of the release TB4 will be reported.